tbuckley/cabot-search huggingface dataset:
Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease
Authors: Georg Semmler, Christian Datz, Michael Trauner
Journal: Clinical and Molecular Hepatology (2022)

Nutrition and dietary interventions are a central component in the pathophysiology, but also a cornerstone in the management of patients with non-alcoholic fatty liver disease (NAFLD). Summarizing our rapidly advancing understanding of how our diet influences our metabolism and focusing on specific effects on the liver, we provide a comprehensive overview of dietary concepts to counteract the increasing burden of NAFLD. Specifically, we emphasize the importance of dietary calorie restriction independently of the macronutrient composition together with adherence to a Mediterranean diet low in added fructose and processed meat that seems to exert favorable effects beyond calorie restriction. Also, we discuss intermittent fasting as a type of diet specifically tailored to decrease liver fat content and increase ketogenesis, awaiting future study results in NAFLD. Finally, personalized dietary recommendations could be powerful tools to increase the effectiveness of dietary interventions in patients with NAFLD considering the genetic background and the microbiome, among others.
The independent effect of exercise on biopsy-proven non-alcoholic fatty liver disease: A systematic review
Authors: George Chen, Bubu Banini, Albert Do, Joseph K. Lim
Journal: Clinical and Molecular Hepatology (2022)

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Although previous studies have demonstrated that exercise independently reduces hepatic steatosis measured by imaging modalities in NAFLD, the effect of exercise on histological endpoints remains unclear. We aimed to conduct a systematic review of the independent effect of exercise on hepatic steatosis, steatohepatitis, and liver fibrosis as measured by histological assessment or non-invasive tests (NITs) in biopsy-proven NAFLD. A systematic literature search of PubMed, Embase, and Web of Science databases was performed using keywords related to exercise, NAFLD, and biopsy. Articles were selected based on the following inclusion criteria: (1) involved human subjects with biopsy-proven NAFLD, (2) analyzed the independent effect of exercise, (3) assessed changes in hepatic steatosis, steatohepatitis, or liver fibrosis via either histological evaluation or NITs, and (4) were original research studies. We identified a total of six studies that analyzed the independent effect of exercise on histological endpoints in biopsy-proven NAFLD. Two randomized controlled trials (RCTs) did not detect significant histological improvement following exercise interventions, while other non-randomized interventional studies showed that exercise reduces hepatocyte ballooning and liver fibrosis. In addition, five studies assessed NIT outcomes, collectively demonstrating that exercise improves hepatic steatosis measured by magnetic resonance imaging-based techniques but not serum biomarkers for steatohepatitis and liver fibrosis. Additional large RCTs and meta-analyses are warranted to investigate the independent effect of exercise on histological and clinical outcome endpoints in NAFLD.
Global incidence and prevalence of nonalcoholic fatty liver disease
Authors: Margaret LP Teng, Cheng Han Ng, Daniel Q. Huang, Kai En Chan, Darren JH Tan, Wen Hui Lim, Ju Dong Yang, Eunice Tan, Mark D. Muthiah
Journal: Clinical and Molecular Hepatology (2022)

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.
Risk factors in nonalcoholic fatty liver disease
Authors: Eunji Ko, Eileen L. Yoon, Dae Won Jun
Journal: Clinical and Molecular Hepatology (2022)

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, with a global prevalence estimated at approximately 25%. NAFLD is also the leading cause of liver cirrhosis, hepatocellular carcinoma, and death. Additionally, the risk of cardiovascular disease increases with greater NAFLD severity. The liver- and cardiovascular disease-related mortality incident rate ratios among the NAFLD population were 0.77 and 4.79 per 1,000 person-years, respectively. We intend to discuss the risk factors associated with NAFLD in terms of development and progression. Obesity or higher body mass index is closely associated with NAFLD in a dose-dependent manner, but growing evidence suggests that central obesity plays a more important role in the development of NAFLD. Saturated fat and fructose have been reported to be closely related to NAFLD. Fructose intake promotes lipogenesis and impairs mitochondria fat oxidation. The presence of type 2 diabetes is the most powerful predictive risk factor for hepatic fibrosis in patients with NAFLD. Single nucleotide polymorphism is not only associated with the prevalence of NAFLD but also associated with increased liver disease mortality. Obstructive sleep apnea, intestinal dysbiosis, and sarcopenia are associated with the development of NAFLD
Endoscopic full-thickness resection preserving the mucosa: more is better
Authors: Miao Shi, Jiyu Zhang, Saif Ullah, Dan Liu
Journal: Endoscopy (2022)

A 60-year-old woman with a submucosal tumor originating from the muscularis propria located in the gastric fornix ([Fig. 1 a]) was referred to our hospital. Contrast-enhanced computed tomography (CT) showed a well-defined and low-density mass close to the cardia ([Fig. 1 b]). Owing to its hard-to-reach location, we decided to perform an optimized gastric endoscopic full-thickness resection (EFTR). This method preserved all the residual mucosa to achieve tension-free closure. After a submucosal saline injection, a 1.5-cm incision was made at the edge of the lesion ([Fig. 1 c]). In the current method, we performed a submucosal dissection to simultaneously create a tunnel ([Fig. 2], [Video 1]). Direct advancement of the endoscope into the fundus tunnel was performed, and the lesion was completely retrieved without removing any of the mucosal layers ([Fig. 1 d]). A full-thickness defect was exposed after removing the mass through the tunnel ([Fig. 1 e]). Subsequently, two edges of the remaining mucosa were easily clipped together ([Fig. 1 f, g]). The total wound closure time closure was 6 minutes. The submucosal tumor measured 25 mm at the highest diameter externally ([Fig. 1 h]). Postoperatively, the patient remained asymptomatic and was discharged on the third day without any complications.
Endoscopic ultrasound-guided drainage of a liver abscess with a self-expandable metal stent as rescue therapy after plastic stent misdeployment
Authors: Esteban Fuentes-Valenzuela, Beatriz Burgueño Gomez, Carlos Chavarría, Ramon Sanchez-Ocana, Carlos de la Serna-Higuera, Manuel Perez-Miranda
Journal: Endoscopy (2022)

Endoscopic ultrasound (EUS) is an alternative to percutaneous drainage of abdominal abscesses [1]. Percutaneous abscess drainage may be challenging in poorly accessible locations [2].
Three pancreatic duct lesions in one patient found at an early stage by cholangioscopy
Authors: Wengang Zhang, Ningli Chai, Yaqi Zhai, Shengzhen Liu, Huikai Li, Fei Gao, Enqiang Linghu
Journal: Endoscopy (2022)

A 49-year-old woman with a common bile duct (CBD) stone underwent preoperative magnetic resonance cholangiopancreatography (MRCP) at our hospital. This showed cholangiectasis, the CBD stone, and filling defects in the proximal and middle pancreatic duct (PD) ([Fig. 1]). Endoscopic retrograde cholangiopancreatography (ERCP) was performed, therefore, and the CBD stone was removed successfully; subsequently, the PD was intubated and the filling defect in the mid-PD was confirmed by pancreatography.
A single-shot ChAd3-MARV vaccine confers rapid and durable protection against Marburg virus in nonhuman primates
Authors: Ruth Hunegnaw, Anna N. Honko, Lingshu Wang, Derick Carr, Tamar Murray, Wei Shi, Lam Nguyen, Nadia Storm, Caitlyn N. M. Dulan, Kathryn E. Foulds, Krystle N. Agans, Robert W. Cross, Joan B. Geisbert, Cheng Cheng, Aurélie Ploquin, Daphne A. Stanley, Thomas W. Geisbert, Gary J. Nabel, Nancy J. Sullivan
Journal: Science Translational Medicine (2022)

Marburg virus (MARV) causes a severe hemorrhagic fever disease in primates with mortality rates in humans of up to 90%. MARV has been identified as a category A bioterrorism agent by the Centers for Disease Control and Prevention (CDC) and priority pathogen A by the National Institute of Allergy and Infectious Diseases (NIAID), needing urgent research and development of countermeasures because of the high public health risk it poses. The recent cases of MARV in West Africa underscore the substantial outbreak potential of this virus. The potential for cross-border spread, as had occurred during the 2014–2016 Ebola virus outbreak, illustrates the critical need for MARV vaccines. To support regulatory approval of the chimpanzee adenovirus 3 (ChAd3)–MARV vaccine that has completed phase 1 trials, we showed that the nonreplicating ChAd3 vector, which has a demonstrated safety profile in humans, protected against a uniformly lethal challenge with MARV/Ang. Protective immunity was achieved within 7 days of vaccination and was maintained through 1 year after vaccination. Antigen-specific antibodies were an immune correlate of protection in the acute challenge model, and their concentration was predictive of protection. These results demonstrate that a single-shot ChAd3-MARV vaccine generated a protective immune response that was both rapid and durable with an immune correlate of protection that will support advanced clinical development.
Ultra-Processed Food Consumption and Increased Risk of Metabolic Syndrome in Adults: The ELSA-Brasil
Authors: Scheine Leite Canhada, Álvaro Vigo, Vivian Cristine Luft, Renata Bertazzi Levy, Sheila Maria Alvim Matos, Maria del Carmen Molina, Luana Giatti, Sandhi Barreto, Bruce Bartholow Duncan, Maria Inês Schmidt
Journal: Diabetes Care (2022)

OBJECTIVE To investigate the association between ultra-processed food (UPF) consumption and the incidence of metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS From 2008 to 2010, we enrolled 15,105 adults, aged 35–74 years, who were employees from six public education and research institutions to assemble the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We used a food frequency questionnaire to assess UPF consumption (measured in grams per day) at baseline. We then assessed the outcomes of those returning to visits between 2012 and 2014 and between 2017 and 2019. We defined incident MetS by the presence of at least three of the following five abnormalities: high fasting glucose level, high triglyceride level, low HDL cholesterol level, high blood pressure, and abdominal obesity, after excluding those meeting such criteria at baseline. We also excluded those who had missing data or an implausible energy intake, leaving 8,065 participants in the study. RESULTS The median age was 49 years, 59% of participants were women, and the median consumption of UPFs was 366 g/day. After 8 years, there were 2,508 new cases of MetS. In robust Poisson regression, adjusting for sociodemographics, behavioral factors, and energy intake, we found a 7% (relative risk [RR] 1.07; 95% CI 1.05–1.08) higher risk of incident MetS for an increase of 150 g/day in UPF consumption. Similarly, those in the fourth quartile (compared with the first quartile) had a 33% increased risk (RR 1.33; 95% CI 1.20–1.47). Further adjustment for BMI attenuated these associations (for 150 g/day increases in UPF consumption and for the fourth quartile compared to the first one, respectively, RR = 1.04, 95% CI 1.02–1.06; RR = 1.19, 95% CI 1.07–1.32). CONCLUSIONS Greater consumption of UPFs is associated with an increased risk of MetS. These findings have important implications for diabetes and cardiovascular disease prevention and management.
Combination bezafibrate and nivolumab treatment of patients with advanced non–small cell lung cancer
Authors: Kentaro Tanaka, Kenji Chamoto, Sho Saeki, Ryusuke Hatae, Yuki Ikematsu, Kazuko Sakai, Nobuhisa Ando, Kazuhiro Sonomura, Shinsuke Kojima, Masanori Taketsuna, Young Hak Kim, Hironori Yoshida, Hiroaki Ozasa, Yuichi Sakamori, Tomoko Hirano, Fumihiko Matsuda, Toyohiro Hirai, Kazuto Nishio, Takuro Sakagami, Masanori Fukushima, Yoichi Nakanishi, Tasuku Honjo, Isamu Okamoto
Journal: Science Translational Medicine (2022)

Despite the success of cancer immunotherapies such as programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) inhibitors, patients often develop resistance. New combination therapies with PD-1/PD-L1 inhibitors are needed to overcome this issue. Bezafibrate, a ligand of peroxisome proliferator-activated receptor-γ coactivator 1α/peroxisome proliferator-activated receptor complexes, has shown a synergistic antitumor effect with PD-1 blockade in mice that is mediated by activation of mitochondria in T cells. We have therefore now performed a phase 1 trial (UMIN000017854) of bezafibrate with nivolumab in previously treated patients with advanced non-small cell lung cancer. The primary end point was the percentage of patients who experience dose-limiting toxicity, and this combination regimen was found to be well tolerated. Preplanned comprehensive analysis of plasma metabolites and gene expression in peripheral cytotoxic T cells indicated that bezafibrate promoted T cell function through up-regulation of mitochondrial metabolism including fatty acid oxidation and may thereby have prolonged the duration of response. This combination strategy targeting T cell metabolism thus has the potential to maintain antitumor activity of immune checkpoint inhibitors and warrants further validation.
Thalamocortical circuits drive remifentanil-induced postoperative hyperalgesia
Authors: Yan Jin, Yu Mao, Danyang Chen, Yingju Tai, Rui Hu, Chen-Ling Yang, Jing Zhou, Lijian Chen, Xuesheng Liu, Erwei Gu, Chunhui Jia, Zhi Zhang, Wenjuan Tao
Journal: Journal of Clinical Investigation (2022)

Remifentanil-induced hyperalgesia (RIH) is a severe but common postoperative clinical problem with elusive underlying neural mechanisms. Here, we discovered that glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLGlu) exhibited significantly elevated burst firing accompanied by upregulation of Cav3.1 T-type calcium channel expression and function in RIH model mice. In addition, we identified a glutamatergic neuronal thalamocortical circuit in the VPL projecting to hindlimb primary somatosensory cortex glutamatergic neurons (S1HLGlu) that mediated RIH. In vivo calcium imaging and multi-tetrode recordings revealed heightened S1HLGlu neuronal activity during RIH. Moreover, preoperative suppression of Cav3.1-dependent burst firing in VPLGlu neurons or chemogenetic inhibition of VPLGlu neuronal terminals in the S1HL abolished the increased S1HLGlu neuronal excitability while alleviating RIH. Our findings suggest that remifentanil induces postoperative hyperalgesia by upregulating T-type calcium channel-dependent burst firing in VPLGlu neurons to activate S1HLGlu neurons, thus revealing an ion channel–mediated neural circuit basis for RIH that can guide analgesic development.
Cardiac Injury Before and After COVID-19
Authors: Jan Elliot González, Adelina Doltra, Rosario J. Perea, Pau Lapeña, Cora Garcia-Ribas, Jana Reventos, Gala Caixal, Jose Maria Tolosana, Eduard Guasch, Ivo Roca-Luque, Elena Arbelo, Marta Sitges, Susanna Prat-Gonzalez, Lluís Mont, Till F. Althoff
Journal: JACC. Cardiovascular imaging (2022)
Invasive Right Ventricular to Pulmonary Artery Coupling in Patients Undergoing Transcatheter Edge-to-Edge Tricuspid Valve Repair
Authors: Lukas Stolz, Ludwig T. Weckbach, Nicole Karam, Daniel Kalbacher, Fabien Praz, Philipp Lurz, Hazem Omran, Christos Iliadis, Jörg Hausleiter, Michael Näbauer, Thomas J. Stocker, Philipp M. Doldi, Sebastian Ludwig, Benedikt Koell, Mohammad Kassar, Christian Besler, Matthias Unterhuber, Karl-Philipp Rommel, Roman Pfister, Jennifer Eatemadi, Volker Rudolph
Journal: JACC. Cardiovascular imaging (2022)
Dual antibody inhibition of KLK5 and KLK7 for Netherton syndrome and atopic dermatitis
Authors: Joseph Chavarria-Smith, Cecilia P.C. Chiu, Janet K. Jackman, Jianping Yin, Juan Zhang, Jason A. Hackney, Wei-Yu Lin, Tulika Tyagi, Yonglian Sun, Janet Tao, Debra Dunlap, William D. Morton, Swapnil V. Ghodge, Henry R. Maun, Hong Li, Hilda Hernandez-Barry, Kelly M. Loyet, Emily Chen, John Liu, Christine Tam, Brian L. Yaspan, Hao Cai, Mercedesz Balazs, Joseph R. Arron, Jing Li, Arthur J Wittwer, Rajita Pappu, Cary D. Austin, Wyne P. Lee, Robert A. Lazarus, Jawahar Sudhamsu, James T. Koerber, Tangsheng Yi
Journal: Science Translational Medicine (2022)

The epidermis is a barrier that prevents water loss while keeping harmful substances from penetrating the host. The impermeable cornified layer of the stratum corneum is maintained by balancing continuous turnover driven by epidermal basal cell proliferation, suprabasal cell differentiation, and corneal shedding. The epidermal desquamation process is tightly regulated by balance of the activities of serine proteases of the Kallikrein-related peptidases (KLK) family and their cognate inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI), which is encoded by the serine peptidase inhibitor Kazal type 5 gene. Imbalance of proteolytic activity caused by a deficiency of LEKTI leads to excessive desquamation due to increased activities of KLK5, KLK7, and KLK14 and results in Netherton syndrome (NS), a debilitating condition with an unmet clinical need. Increased activity of KLKs may also be pathological in other dermatoses such as atopic dermatitis (AD). Here, we describe the discovery of inhibitory antibodies against murine KLK5 and KLK7 that could compensate for the deficiency of LEKTI in NS. These antibodies are protective in mouse models of NS and AD and, when combined, promote improved skin barrier integrity and reduced inflammation. To translate these findings, we engineered a humanized bispecific antibody capable of potent inhibition of human KLK5 and KLK7. A crystal structure of KLK5 bound to the inhibitory Fab revealed that the antibody binds distal to its active site and uses a relatively unappreciated allosteric inhibition mechanism. Treatment with the bispecific anti-KLK5/7 antibody represents a promising therapy for clinical development in NS and other inflammatory dermatoses.
Extracellular matrix-based sticky sealants for scar-free corneal tissue reconstruction
Authors: Hyeonji Kim, Je-Hwan Jang, Wonil Han, Hyun-Jeong Hwang, Jinah Jang, Joon Young Kim, Dong-Woo Cho
Journal: Biomaterials (2022)

Regenerative medicine requires both tissue restoration and ease of compliance for clinical application. Considering this, sticky tissue sealants have been shown to have great potentials over surgical suturing and wound treatment. However, tissue sealants currently used pose challenges such as uncontrollable adhesion formation, mechanical mismatch, and lack of tissue restoration. A new sticky sealant based on gelatinized cornea-derived extracellular matrix (GelCodE) with a visible light-activating system is firstly being introduced in this study. De novo tissue regeneration relies on the matrisome in charge of tissue-organization and development within GelCodE while visible light-based photopolymerization with ruthenium/sodium persulfate rapidly induces covalent bonds with the adjacent tissues. The ease of not only in vivo application, biocompatibility, and biointegration, but also exceptional de novo tissue formation is demonstrated in this study. Interestingly, newly regenerated tissues were shown to have normal tissue-like matrices with little scar formation. Hence, this work presents a promising strategy to meet clinical demands for scar-free tissue recovery with superior ease of clinical application.
SARS-CoV-2 viral protein ORF3A injures renal tubules by interacting with TRIM59 to induce STAT3 activation
Authors: Hong Cai, Ya Chen, Ye Feng, Morad Asadi, Lewis Kaufman, Kyung Lee, Thomas Kehrer, Lisa Miorin, Adolfo Garcia-Sastre, G. Luca Gusella, Leyi Gu, Zhaohui Ni, Shan Mou, John Cijiang He, Weibin Zhou
Journal: Molecular Therapy (2022)

Acute kidney injury occurs frequently in COVID-19 patients infected by the coronavirus SARS-CoV-2, and infection of kidney cells by this virus has been reported. However, little is known about the direct impact of the SARS-CoV-2 infection upon the renal tubular cells. We report that SARS-CoV-2 activated signal transducer and activator of transcription 3 (STAT3) signaling and caused cellular injury in the human renal tubular cell line. Mechanistically, the viral protein ORF3A of SARS-CoV-2 augmented both NF-κB and STAT3 signaling and increased the expression of kidney injury molecule 1. SARS-CoV-2 infection or expression of ORF3A alone elevated the protein level of tripartite motif-containing protein 59 (TRIM59), an E3 ubiquitin ligase, which interacts with both ORF3A and STAT3. The excessive TRIM59 in turn dissociated the phosphatase TCPTP from binding to STAT3 and hence inhibited the dephosphorylation of STAT3, leading to persistent STAT3 activation. Consistently, ORF3A induced renal injury in zebrafish and mice. In addition, expression of TRIM59 was elevated in the kidney autopsies of COVID-19 patients with acute kidney injury. Thus, the aberrant activation of STAT3 signaling by TRIM59 plays a significant role in the renal tubular cell injury caused by SARS-CoV-2, which suggests a potential targeted therapy for the renal complications of COVID-19. Acute kidney injury occurs frequently in COVID-19 patients infected by the coronavirus SARS-CoV-2, and infection of kidney cells by this virus has been reported. However, little is known about the direct impact of the SARS-CoV-2 infection upon the renal tubular cells. We report that SARS-CoV-2 activated signal transducer and activator of transcription 3 (STAT3) signaling and caused cellular injury in the human renal tubular cell line. Mechanistically, the viral protein ORF3A of SARS-CoV-2 augmented both NF-κB and STAT3 signaling and increased the expression of kidney injury molecule 1. SARS-CoV-2 infection or expression of ORF3A alone elevated the protein level of tripartite motif-containing protein 59 (TRIM59), an E3 ubiquitin ligase, which interacts with both ORF3A and STAT3. The excessive TRIM59 in turn dissociated the phosphatase TCPTP from binding to STAT3 and hence inhibited the dephosphorylation of STAT3, leading to persistent STAT3 activation. Consistently, ORF3A induced renal injury in zebrafish and mice. In addition, expression of TRIM59 was elevated in the kidney autopsies of COVID-19 patients with acute kidney injury. Thus, the aberrant activation of STAT3 signaling by TRIM59 plays a significant role in the renal tubular cell injury caused by SARS-CoV-2, which suggests a potential targeted therapy for the renal complications of COVID-19.